Lipin-1 is a novel substrate of protein phosphatase PGAM5
Lipin-1 is a novel substrate of protein phosphatase PGAM5
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DOI：
10.1016/j.bbrc.2019.01.031
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发表时间：
2019-02-19
影响因子：
3.1
通讯作者：
Ishimoto, Kenji
中科院分区：
文献类型：
--
作者：
Okuno, Hiroko;Okuzono, Haruna;Ishimoto, Kenji
Lipin-1 具有多种功能，根据其亚细胞定位调节脂质和能量代谢。 Lipin-1 的亚细胞定位由激酶依赖性磷酸化决定；然而，使 Lipin-1 去磷酸化和失活的磷酸酶仍然难以捉摸。使用免疫沉淀和 LC-MS/MS 方法，我们鉴定了磷酸甘油酸变位酶家族成员 5 (PGAM5)，一种丝氨酸/苏氨酸特异性蛋白磷酸酶，作为 Lipin-1 活性的调节剂。用羰基氰间氯苯腙 (CCCP) 处理人肝细胞癌细胞，可激活内源性 PGAM5，促进 Lipin-1 的去磷酸化和核积累。我们的研究结果进一步阐明了调节 Lipin-1 的分子机制。 (C) 2019 Elsevier Inc. 保留所有权利。
Lipin-1 has multiple functions that regulate lipid and energy metabolism according to its subcellular localization. The subcellular localization of Lipin-1 is determined by kinase-dependent phosphorylation; however, the phosphatase that dephosphorylates and inactivates Lipin-1 has remained elusive. Using an immunoprecipitation and LC-MS/MS approach we have identified phosphoglycerate mutase family member 5 (PGAM5), a serine/threonine specific protein phosphatase, as a regulator of Lipin-1 activity. Treatment of human hepatocellular carcinoma cells with carbonyl cyanide m-chlorophenyl hydrazone (CCCP), which activates endogenous PGAM5, promoted dephosphorylation and nuclear accumulation of Lipin-1. Our findings further elucidate the molecular mechanisms that regulate Lipin-1. (C) 2019 Elsevier Inc. All rights reserved.